At fertilization, or upon artificial stimulation, physiological changes occur in the zona pellucida of the murine eggs that render it impermeable to supernumerary sperm. This is the major source of block to polyspermy in the mouse. In addition to becoming impermeable to supernumerary sperm the zona pellucida also becomes resistant (hardened) to dissolution by proteases. Here, we demonstrated for the first time a direct relationship between the age of cumulus-free oocytes and their increased resistance to digestion with Alpha-chymotrypsin, independent of fertilization-associated cortical reaction. Futhermore, concomitant with the decrease in zona solubility there is a decrease in fertilizability of the cumulus-free oocytes. Zygotes from cumulus-free in vitro fertilized oocytes develop at a reduced rate into blastocysts. We also demonstrated that development of mouse oocytes can be initiated through exposure to alcohol. In these oocytes meiosis is completed, cortical reaction occurs which is then subsequently followed by the hardening of the zona pellucida. In this respect alcohol treatment of mouse oocytes may best resemble the activation of development normally accomplished by the fertilizing sperm.